Gene Expression Profiling in Peripheral Blood Mononuclear Cells of Patients with Common Variable Immunodeficiency: Modulation of Adaptive Immune Response following Intravenous Immunoglobulin Therapy

Abstract

BackgroundRegular intravenous immunoglobulin treatment is used to replace antibody deficiency in primary immunodeficiency diseases; however the therapeutic effect seems to be related not only to antibody replacement but also to an active role in the modulation of the immune response. Common variable immunodeficiency is the most frequent primary immunodeficiency seen in clinical practice.MethodsWe have studied the effect of intravenous immunoglobulin replacement in patients with common variable immunodeficiency by evaluating the gene-expression profiles from Affimetrix HG-U133A. Some of the gene array results were validated by real time RT-PCR and by the measurement of circulating cytokines and chemokines by ELISA. Moreover we performed FACS analysis of blood mononuclear cells from the patients enrolled in the study.ResultsA series of genes involved in innate and acquired immune responses were markedly up- or down-modulated before therapy. Such genes included CD14, CD36, LEPR, IRF-5, RGS-1, CD38, TNFRSF25, IL-4, CXCR4, CCR3, IL-8. Most of these modulated genes showed an expression similar to that of normal controls after immunoglobulin replacement. Real time RT-PCR of selected genes and serum levels of IL-4, CXCR4 before and after therapy changed accordingly to gene array results. Interestingly, serum levels of IL-8 remained unchanged, as the corresponding gene, before and after treatment. FACS analysis showed a marked decrease of CD8+T cells and an increase of CD4+T cells following treatment. Moreover we observed a marked increase of CD23−CD27−IgM−IgG− B cells (centrocytes).ConclusionsOur results are in accordance with previous reports and provide further support to the hypothesis that the benefits of intravenous immunoglobulin therapy are not only related to antibody replacement but also to its ability to modulate the immune response in common variable immunodeficiency.

Loss of Circulating Mucosal-Associated Invariant T Cells in Common Variable Immunodeficiency Is Associated with Immune Activation and Loss of Eomes and PLZF

“…3C). The loss of overall CD4 + T cells in CVID patients is well documented (13,(35)(36)(37), and we found that CD4 + T cells were reduced also in this cohort (data not shown). This suggests that the subset of CD4 + T cells expressing CD161 is specifically preserved in CVID patients.…”

“…It is unknown why CD161 + CD4 + T cells were preserved in CVID, unlike the general loss of CD4 + T cells, which has been well documented (13,(35)(36)(37). This would suggest that CD161 expression identifies a subset of CD4 + T cells that is preserved in CVID.…”

Gene Expression Profiles in Primary Sjögren's Syndrome With and Without Systemic Manifestations

“…The significantly different expression of genes observed in microarray assay was validated by testing some selected genes with real‐time polymerase chain reaction (RT‐PCR) in patients and healthy controls. The method adopted for this validation procedure is detailed in the Supplementary section .…”

T-Cell Abnormalities in Common Variable Immunodeficiency

“…However, Artac et al [96] reported that expression of CD69 and HLA-DR by CD8 + T cells is not affected by IVIG. The immunological mechanisms by which IVIG can normalize T-cell counts and function in CVID patients remains unclear, but Dolcino et al [97] reported that lower expression of LEPR, a major gene in CD4 + T-cell proliferation, returned to normal values after IVIG treatment [97]. Artac et al also showed that IVIG causes an increase in the expression of CD95 and CD25 in CVID patients and suggested that CD95 may play a critical role in the effects of IVIG for control of autoimmunity and inflammation in CVID patients.…”